Pre-eclampsia is a multisystem disorder that complicates 10 percent of pregnancies. This disease leads to increased morbidity and mortality for both the mother and baby. Although the clinical presentation of the disease is well described, the pathophysiologic mechanisms for the clinical manifestations are not. The overall hypothesis of this application is that vascular endothelial growth factor (VEGF) and placental growth factor (PIGE) are likely mediators of some of the clinical features of preeclampsia and the placenta is the site for the altered production of these growth factors. VEGF and PIGF are specific mitogen for endothelial cells and are potent stimuli for angiogenesis and vascular permeability. The biological activity of these related growth factors is modified depending on the concentration of each. This proposal will examine their relationship to the clinical manifestations of preeclampsia in two specific aims. In specific aim one, the hypothesis to be tested is that maternal serum levels of PIGE and VEGF are altered in preeclamptic patients and these alterations correlate to increased vascular permeability and subsequently clinical manifestations of the disease, such as proteinuria and pulmonary edema. Maternal serum levels of VEGF and PIGE will be measured by enzyme-linked immunosorbent assay (ELISA) in pregnancies complicated by pre-eclampsia and then compared to those found in normal pregnancies. We will follow patients longitudinally to determine if the alterations of VEGF and PIGF change as the disease progresses. PIGF is an important modulator of VEGF activity. We predict that PIGE levels decrease but VEGF levels remain unchanged or increase. As PIGF levels become more depressed, the clinical manifestations of preeclampsia will progress. In specific aim two, the hypothesis to be tested is that alterations in maternal serum levels of PIGF and VEGF will be reflected in the placenta at the level of gene expression. Maternal serum levels of VEGF and PIGE will be measured by ELISA in normal pregnancies and pregnancies complicated by pre-eclampsia and correlated with the expression VEGF and PIGE mRNA in the placenta determined by Northern blot. The placenta is likely the major source for these growth factors in pregnancy and any changes in the serum levels will be reflected in the placenta. In other words PIGF gene expression will be reduced and VEGF gene expression will be unchanged or increased.